Clusterin is a glycoprotein markedly induced in the kidney following renal injury. We hypothesize that clusterin functions to protect cells from injury either by promoting cell/cell or cell/matrix interactions or by complexing and inactivating potentially injurious extracelluar substances. In Specific Aim 1 we will test the hypothesis that clusterin is protective against renal epithelial cell injury using an in vitro system of inducible over expression of clusterin in renal epithial cells and an in vivo system of injury in clusterin deficient mice. In Specific Aim 2a we will test the hypothesis that protective function of clusterin is mediated by its promotion of cell/cell or cell/matrix interactions. In Specific Aim 2b we will test the hypothesis that the protective function of clusterin is mediated by its ability to complex and inactivate potentially toxic extracellular substances.